Brief description of study

The primary objective of this study is to demonstrate that the combination of palbociclib
with anti-HER2 therapy plus endocrine therapy is superior to anti-HER2-based therapy plus
endocrine therapy alone in improving the outcomes of subjects with hormone receptor-positive,
HER2+ metastatic breast cancer.

Detailed Study Description

Subjects will be randomized into one of two treatment arms following minimum of 4 and maximum
of 8 cycles of induction treatment with anti-HER2 therapy. Arm A subjects will receive the
experimental therapy, palbociclib, in addition to their current anti-HER2 therapy and
endocrine therapy. Arm B subjects will continue to receive the anti-HER2 therapy. It is
expected that the addition of palbociclib to the first-line treatment of HER2 disease will
delay the onset of therapeutic resistance and ultimately prolong the survival of patients
with metastatic breast cancer. The study is designed to treat the subset of patients with
HER2+ disease who are also hormone receptor positive (HR+). It is also expected that
palbociclib will modulate the endocrine resistance in HER2+/HR+ disease and potentiate the
benefits of anti-HER2 therapy. Lastly, the current study includes a comprehensive molecular
characterization of the disease at study entrance which will allow us to investigate the
benefits of palbociclib in subsets of HER2+/HR+ disease such as PIK3CA mutant.